Nothing explains the aluminum free ion Al3+ more intelligently than the following:
The likely principal antagonist in all such events is Al3+ (aq) and its mechanism of action will involve numbers of different agents or intermediates. For example, we know that aluminium is a potent pro-oxidant, its interaction with the superoxide radical anion establishing, fuelling and sustaining redox cycles. The potency of these effects are all the more significant in that the enhanced formation of reactive oxygen species may be accelerated at sites which are distinct and divorced from locations housing the cell’s anti-oxidant machinery.
For example, aluminium sinks such as the extracellular senile plaques of Aβ42 and the intracellular chromatin of neuronal nuclei are both likely targets of aluminium-driven oxidative damage.
Aluminium is an excitotoxin and a number of mechanisms have been described, whereby aluminium induces elevated and sustained levels of intracellular Ca2+ with significant implications not only for cellular energy metabolism, but also uncontrolled phosphorylation of biomolecules. The presence of biologically reactive aluminium imposes an immediate energy requirement upon a neuron, whether simply because of the need to produce more Ca2+-buffering proteins or because of the requirement to clean-up the consequences of hyperphosphorylation, for example, through autophagosomal activities.
Aluminium is a mutagen and the phosphate-rich environment of the nucleus predisposes it to the accumulation of aluminium and subsequent alterations in the expression of genetic materials. The latter may be subtle but sufficient to bring about significant alterations in neuronal physiology over extended time periods.
Aluminium is, of course, a powerful immunogen, being the preferred adjuvant in vaccination and immunotherapy. This activity as an adjuvant, and concomitantly as an antigen, at injection sites in skin or muscle must also be considered for focal accumulations of aluminium within the CNS and such reactivity may underlie aluminium’s suggested roles in autoimmunity...read more>>>...
